Quantities of racemic and optically active perhydrohistrionicotoxins have been prepared by total synthesis. The (-)-enantiomer proved to be identical with the naturally derived material. The finding that (+)-2-desamylperhydro-histrionicotoxin has the same biological activity as (+)-H12-HTX led to an investigation regarding structure-activity-relationship showing that the presence of a basic amine function properly spaced to the alcohol or ketone moiety was important to find activity in vitro. The (+)-2-desamyl derivative was not very toxic to mice.